Haemostasis and thrombosis Flashcards
What do haemostasis and thrombosis characterise? How are they catagorised?
Haemostasis - appropriate coagualtion - primary and secondary
Thrombosis - over coagulation - arterial and venous
WHat are the componants of fresh whole blood? Importantly what do these componants contain?
Platelets
Plasma - CONTAINS ALL CLOTTING FACTORS
Red and white cells
What occurs immediately upon vessel injury?
What does this ultimately cause
1) Platelet adhesion (platelet aggregation)
2) Activation of coagulation cascade (fibrin formation)
Ultimately leads to formation of haemostatic plug and fibrinolytic activity which leads to repair of vessel damage
Steps of primary haemostasis?
1) Injury to vessel wall –> exposure of collagen
2) Platelets adhere to collagen via VWF and receptors on their membrane
3) vWF will then bind other receptors and activate other receptors which causes further aggregation forming a platelet plaque
What occurs when primary heamostasis doesn’t occur/is dyasfunctional?
Excessive bleeding
Bleeding disorders - 2 types - characterised by?
Main treatment used
Reduced number of platelets
Inherited or acquired
Platelet transfusion used –> give the patient platelets which is then infused into the blood to allow proper aggregation
VON WILLEBRAND DISEASE - what is this caused by? What is the disease therefore characterised by?
Most common bleeding disorder
Missing VWF on platelets - platelets therefore cannot stick to collagen
Causes easy bruising, bleeding at gums, epistaxis, post operative trauma
Von willebrand disease - types and treament
Autosomal dominant - 3 main types with many sub types. Milder in general than haemophilia.
Treatment using DESMOPRESSIN - stimulates release of VWF from endothelial cells
OR Plasma derived clotting factor (IV administration)
Steps to secondary haemostasis - main enzymes - what is the analogy for primary and secondary steps
THROMBIN - FACTOR ||a –> key enzymes!
Analogy - ruptured blood vessel - primary is the plasters / the sticky part - VWF – on a large scale, this isn’t that strong
Secondary is like spraying the VWF with superglue –> the strong part
Action of clotting factor ||a / Thrombin?
Converts fibrinogen (liquid) to fibrin (mesh/solid which stops the bleeding)
Coagulation factor disorders - genetic type?
Haemophilia A - x linked (clotting factor 8 deficient)
Haemophilia B - x linked (clotting factor 9 deficient)
Autosomal recessive haemophilia? how is treatment of haemophilia personalised?
Autosomal recessive characterised by a deficiency in fibrinogen
Can take a more personalised approach by handing out a particular clotting factor to a patient that is deficient in that particular factor
Haemophilia - types a and b - sex linked heritage? What is the normal level of Fibrinogen and how does this allow sub categorisation of haemophilia categories
Haemophilia types A and B have identical clinical features
Men have the disease, women are the carriers, 2 copies needed for women to inherit.
Can sub categorise based on severity of how much fibrinogen the patient has: (normal amount is 50-150%)
- <1% of factor = severe
- 1-5% = moderate
- >5% = mild
Haemophilia - types a and b - Where are the sites of trauma? What can it lead to?
Huge bleeds in joints can result
Severe joint damage can arise due to haemothroses (cartilage erodes away and can sometimes end up in the need for joint replacement)
Muscle haematoma - after injury –> intramuscular injection can cause bleeding
Clotting factor concentrates - how is this a form of personalised medicine?
What is available already?
Can give the patient the precise clotting factor that they are missing
Factors can be plasma derived or made using recombinant technology
- Now have them available for factors 8, 9 and 13. Not a large demand for other factors as disease not generally impacting these. Not worth company investment therfore
